CNP, the Third Natriuretic Peptide: Its Biology and Significance to the Cardiovascular System

SIMPLE SUMMARY: CNP is the third natriuretic peptide to be isolated and is widely expressed in the central nervous system, osteochondral system, and vascular system. The receptor that is mainly targeted by CNP is GC-B, which differs from GC-A, the receptor targeted by the other two natriuretic peptides, ANP and BNP. Consequently, the actions of CNP differ somewhat from those of ANP and BNP. Research into the actions of CNP has shown that CNP attenuates cardiac remodeling in animal models of cardiac hypertrophy, myocardial infarction, and myocarditis. Studies examining CNP/GC-B signaling showed that it contributes to the prevention of cardiac stiffness. Endogenous CNP, perhaps acting in part through CNP/NPR-C signaling, contributes to the regulation of vascular function and blood pressure. CNP regulates vascular remodeling and angiogenesis via CNP/GC-B/CGK signaling. CNP attenuates interstitial fibrosis and fibrosis-related gene expression in pressure overload and myocardial infarction models. The clinical application of CNP as a therapeutic agent for cardiovascular diseases is anticipated. ABSTRACT: The natriuretic peptide family consists of three biologically active peptides: ANP, BNP, and CNP. CNP is more widely expressed than the other two peptides, with significant levels in the central nervous system, osteochondral system, and vascular system. The receptor that is mainly targeted by CNP is GC-B, which differs from GC-A, the receptor targeted by ANP and BNP. Consequently, the actions of CNP differ somewhat from those of ANP and BNP. CNP knockout leads to severe dwarfism, and there has been important research into the role of CNP in the osteochondral system. As a result, a CNP analog is now available for clinical use in patients with achondroplasia. In the cardiovascular system, CNP and its downstream signaling are involved in the regulatory mechanisms underlying myocardial remodeling, cardiac function, vascular tone, angiogenesis, and fibrosis, among others. This review focuses on the roles of CNP in the cardiovascular system and considers its potential for clinical application in the treatment of cardiovascular diseases.